Every day thousands of scientists around the world sequence and analyze millions of genetic data. In clinical practice, the information they compile is used to determine possible somatic mutations that could play a role in the diagnosis, prognosis and treatment of diseases. The DNA sequencing of a tumor can be done in three different ways: analyzing the entire genome, reading only the genome’s coding portion (exome) or through panels. The third option is the most sensitive, as it detects the fewest false positives.
But despite a better cost-benefit ratio, sequencing through panels is not exempt from problems. On one hand, the options available on the market are limited. TruSight Amplicon Cancer Panel by Illumina, Gene Read DNAseq Targeted Panels v2 by QIAGEN or xGen® Pan-Cancer Panel from Integrated DNA Technologies are a few of the most widely-marketed, best-known panels. According to Carlota Rubio-Pérez and Abel González-Pérez in Genética Médica, “these panels are non-specific, since they are normally conceived to detect mutations present in any type of tumor, or large groups of them,”
OncoPad, the platform to rationally design sequencing panels
To solve this problem, and respond to specific questions for every case and type of tumor, it was sought to develop a more rational design of sequencing panels. With that goal in their sights, scientists of the Biomedical Genomics group at Pompeu Fabra University and the Hospital del Mar Medical Research Institute have created an open web platform. The tool, which they have named OncoPad, facilitates the design of sequencing panels that are specific for one type of tumor or various forms of cancer simultaneously. Their work has been published in the journal Genome Medicine.
OncoPad identifies the best candidates for the design of a specific panel, based on the known associations between genes and cancer development mechanisms or drug response against it and maximizing its cost/benefit ratio. That way, as they state in the article, they do not take a “one size fits all” approach but rather adapt to specific factors. In order to develop OncoPad, UPF and IMIM researchers collected data from a cohort of 6,792 samples representing 28 different types of cancer, which had been previously gathered by the Rubio-Pérez and Tamborero group and published in the journal Cancer Cell. They also added information from a cohort of 506 samples from chronic lymphocytic leukemia patients. On another note, the candidate genes were selected from the Cancer Drivers Database or the Cancer Gene Census in addition to gathering the genetic information on already-validated oncogenic mutations, including the mutations in non-coding regions associated with chronic lymphocytic leukemia.
Source: Shaury Nash (Flickr)
According to the currently published literature, there are only three tools in the world that facilitate improvement of the rational panel design. Nonetheless, OncoPad is the first platform open to the entire scientific community that makes it possible to design sequencing panels applicable in oncology. Among its possible applications, scientists have outlined a number of hypothetical cases; for example, a researcher seeks to create a panel from a specific list of genes for early detection and stratification of a tumor or the characterization of a cellular line, or if they wish to design a panel to know the response of a cell culture or cancerous samples to a certain antitumor drug. According to Abel González and Núria Lòpez-Bigas, study leaders, “because of the key need it covers, and its ease of use, OncoPad could become a tool used frequently by clinical and translational oncology researchers.”
Genomics has changed research, as well as the diagnosis and treatment of many diseases. For example, in the case of cancer, DNA analysis has made it possible to reach the first molecular consensus on colorectal tumors. Its application in this type of work, nonetheless, also faces significant challenges due to the heterogeneity found in the various genomic studies performed up to now. The creation of a platform like OncoPad will help scientists to more effectively carry out their DNA analyses, achieving a more rational design of the sequencing panels. This goal will work in the mid and long term to improve the use of genomic data in daily clinical practice, especially in the cases of diagnosis, prognosis and treatment of cancer.